Cardiac Arrhythmia in Thalassaemia
Limassol, 24 – 26 October 2012
Malcolm Walker
University College and the Heart Hospitals, London
Clinical Director Hatter Cardiovascular Institute
Cardiac Arrhythmias in thalassaemia
• Plan of talk
1.
2.
3.
4.
5.
Historical aspects
Relationship to iron overload
Clinical Management: Principles & Investigation
Specific arrhythmia
Technology: Ablation & Devices
Malcolm Walker TIF 2012
Cardiac Arrhythmia in thalassaemia
1. Historical aspects
Malcolm Walker TIF 2012
History: incidence of arrhythmia & ECG changes
thalassaemia, transfused but not chelated
Age
Normal ECG %
LV hypertrophy
%
Rhythm
abnormality %
Heart block %
5-10
67
33
6
6
11-15
39
28
44
6
16-20
30
40
50
40
21-30
12
62
19
19
TOTAL
39
40
27
14
Malcolm Walker TIF 2012
Adapted from Ehlers et al 1980
Cardiac Arrhythmia in thalassaemia
2. Relationship to
iron overload
Malcolm Walker TIF 2012
Arrhythmia and myocardial iron assessed by
cMR T2*
● 652 patients with b-thalassaemia
● Mean age 27 yr
● Excluded those with heart failure (HF) at first scan
Malcolm Walker TIF 2012
Arrhythmia and myocardial iron assessed by
cMR T2*
Threshold for arrhythmia
T2*<20ms
Types & frequency:
● AF
78 (12%)
● SVT
14 (2%)
● VT
5 (<1%)
● VF
1
MIOT study group: gender differences
Italian MIOT Cohort
Frequency %
25
20
p=0.14
15
10
5
W
M
en
LV
D
ys
fu
om
nc
tio
en
n
LV
D
ys
fu
nc
tio
n
M
en
ar
rh
yt
hm
W
om
ia
en
ar
rh
yt
hm
ia
0
Adapted from: Marsella et.al. Haematologica 2011; 96: 515
Malcolm Walker TIF 2012
MIOT study group: T2* and cardiac arrhythmia
Adapted from: Marsella et.al. Haematologica 2011; 96: 515
Malcolm Walker TIF 2012
Arrhythmia and myocardial iron assessed
by cMR T2*
Conclusions
•Incidence of arrhythmia very
low in this Italian cohort
•25 out of 776 patients (3.2%);
compared to overall 15%
incidence in 1 year (UK cohort;
Kirk et al 2009)
•No statistical relationship with
heart iron by T2* in Italian
group; clear cut risk associated
with T2* in UK cohort (Kirk et
al 2009)
Arrhythmia and myocardial iron assessed
by cMR T2*
Reasons for differences
between Italian and UK
patients?
•Italian cohort more recent
•Overall lower T2*; very few
patients with T2* < 20 ms
•More patients on
combination Rx (DFO + DFP)
AF in thalassaemia major – UCH clinic
• 80 consecutive clinic attenders 2011-2012
 Mean age 38 yr; 51% female
AF current
 History of AF or pAF
 DM
 Thyroid
 Hep C (ever)
 Heart failure in last 12 months

Malcolm Walker TIF 2012
8.75%
33.7%
48.7%
22.0%
15.0%
10.0%
AF in thalassaemia – UCH clinic
% incidence
55
11
10
Heart iron load by current cMR T2*
Malcolm Walker TIF 2012
AF in thalassaemia – UCH clinic
Relationship between iron load & AF
Reasons for differences
between Italian and UK
patients?
T2* ms
P < 0.05
Walker et al unpublished observations
Range 5 to 13 yr ago
AF in thalassaemia – UCH clinic
Relationship between iron load & AF
Reasons for differences
between Italian and UK
patients?
T2* ms
P < 0.05
•Atrial fibrillation (AF) occurs
late in life and reflects past
history, not current iron status
Walker et al unpublished observations
Range 5 to 13 yr ago
AF in thalassaemia – UCH clinic
Risk factors for AF
 Diabetes link


71% of those in AF now have DM
69% of those with a history or pAF have DM
 LA size (by area by ECHO – cMR volumes awaited)

No clear correlation with AF
 Current LV function (systolic, by EF)


No clear correlation with AF
Correlation with previous episode of LV dysfunction
Malcolm Walker TIF 2012
Cardiac Arrhythmia in thalassaemia
3. Clinical Management
principles & investigation
Malcolm Walker TIF 2012
Clinical aspects of arrhythmia in
thalassaemia
• Symptoms




Palpitation
Breathlessness
Dizziness or near fainting
Collapse
• There is a mismatch between symptoms & severity of
arrhythmia
• “Trivial” problems may cause immense anxiety
• Potentially severe arrhythmia may cause only minor
complaints (or no symptoms)
Malcolm Walker TIF 2012
Clinical aspects of arrhythmia in
thalassaemia
• Symptoms
 Palpitation
Breathlessness
 Dizziness or near fainting
 Collapse

 Near fainting, loss of consciousness or collapse
Always need to be taken very seriously
Malcolm Walker TIF 2012
Clinical aspects of arrhythmia in
thalassaemia
• Management requires
1. Diagnosis of the arrhythmia causing the
symptoms


ECG
Holter ambulatory monitor – 24 hr or longer
• Techniques which may be useful



Malcolm Walker TIF 2012
Implantable loop recorder – “Reveal” device
Analysis of repolarisation (QT and JT dispersion)
Electrophysiology study
Clinical aspects of arrhythmia in
thalassaemia – the clinic ECG
Supraventricular
tachycardia SVT
Atrial Fibrillation AF
Ventricular ectopic VE
Malcolm Walker TIF 2012
Clinical aspects of arrhythmia in
thalassaemia
• Management requires
1. Diagnosis of the arrhythmia causing the
symptoms



ECG
Holter ambulatory monitor – 24 hr or longer
Event recorders
• Techniques which may be useful

Malcolm Walker TIF 2012
Implantable loop recorder – “Reveal” device
Clinical aspects of arrhythmia in
thalassaemia – the Holter 24hr ECG
Holter 24 hr ECG
Patient aged 27 yr
Symptom: palpitation + dizziness
Shows Ventricular tachycardia VT
Malcolm Walker TIF 2012
Holter ambulatory ECG screening
• Holter screening failed
to predict 2 patients
•Significant arrhythmia detected in 15%
patients (n=4)
•Holter screening failed to predict 2
patients who went on to have significant
arrhythmia
•30% of the patients with a normal
Holter had symptoms
•CONCLUSION
•Routine screening of TM
population with Holter not
sensitive nor specific
•Need to consider newer
technologies – event
recorders, ILR
Malcolm Walker TIF 2012
From Qureshi et al. Annals NY Acad Sci 2005
Clinical aspects of arrhythmia in
thalassaemia
• Management requires
1. Diagnosis of the arrhythmia causing the
symptoms



ECG
Holter ambulatory monitor – 24 hr or longer
Event recorders
• Techniques which may be useful

Malcolm Walker TIF 2012
Implantable loop recorder – “Reveal” device
Clinical aspects of arrhythmia in
thalassaemia
• Management requires
1. Diagnosis
However, making the ECG diagnosis is not enough
on its own
• Importance of the arrhythmia depends critically
on knowledge of the underlying cardiac status
1.
2.
3.
Malcolm Walker TIF 2012
Ventricular function; structural heart defects
Iron burden (cMR T2*)
Pro-thrombotic tendency
Clinical aspects of arrhythmia in
thalassaemia
• Management requires
1. Precise diagnosis
2. Knowledge of underlying cardiac status


Ventricular function & cardiac structure by ECHO
Iron burden (T2*) by cMR
An ECHO + cMR are URGENT when
1
2
3
Malcolm Walker TIF 2012
Ventricular arrhythmia
Poorly tolerated AF
Symptoms include loss of consciousness/ collapse/ heart
failure
Clinical aspects of arrhythmia in
thalassaemia - conclusions
• ECG
 Necessary baseline at least every 12/12
 At every cardiovascular assessment

It tells us more about the heart than just arrhythmia
• Holter 24hr ECG
 Useful to investigate symptoms
 Poor as a screening tool in asymptomatic well
chelated TM patients with good LV function
Malcolm Walker TIF 2012
Cardiac Arrhythmia in thalassaemia
4. Specific arrhythmia
VT
AF
Malcolm Walker TIF 2012
Specific arrhythmia
Tachycardia – ventricular (VT)
• Ventricular tachycardia (VT) or broad complex
tachycardia
Malcolm Walker TIF 2012
Specific arrhythmia
Tachycardia – ventricular (VT)
• Ventricular tachycardia (VT) or broad complex
tachycardia
 This is a medical emergency


Input of emergency physicians/ cardiologists
Immediate cardioversion if in collapse or shock
 It always complicates severe iron overload
 It may respond to iv chelation with DFO


iv DFO must be started immediately
Combination treatment may be indicated
Malcolm Walker TIF 2012
Specific arrhythmia
Tachycardia – ventricular (VT)
• Ventricular tachycardia (VT) or broad complex
tachycardia
 Once acute event controlled

Consider implantation of ICD
 Poor LV function not improving with iv chelation
 VT occurs without high iron overload – look for another
cause!

ICD must be MRI compatible
Malcolm Walker TIF 2012
Specific arrhythmia
Atrial Fibrillation AF
• AF: the commonest arrhythmia
 Paroxysmal
 Persistent
 Permanent
Malcolm Walker TIF 2012
Specific arrhythmia: Atrial Fibrillation
Risk to patient: Heart Failure
1 Cardiac decompensation/ overt heart failure
Most likely when AF first appears - when heart rate is
high
 Target treatment to:

1.
2.

Control rate
Restore normal sinus rhythm
Check, urgently if significant heart failure signs:
1.
2.
3.
Malcolm Walker TIF 2012
LV function by ECHO
Cardiac iron status by cMR T2*
Thyroid function etc.
Specific arrhythmia: Atrial Fibrillation
Risk to patient: Stroke
2 Stroke risk depends critically on:




Prothrombotic status
Structural heart disease
Impaired LV
Higher risk if AF is persistent or permanent or
frequent paroxysms of more than 12 hr duration
1.
2.

Check
1.
Malcolm Walker TIF 2012
Restore normal sinus rhythm where possible
Anti-coagulation with warfarin (INR 2.5) or new agents
Cardiac ECHO for LA size, LV function, valve disease
Specific arrhythmia
AF – special circumstances
1.
2.
3.
4.
Complicating cardiac failure
Precipitating cardiac failure
In iron loaded TM with good LV function
In non iron loaded TM with good function
Malcolm Walker TIF 2012
Specific arrhythmia
AF – special circumstances
1. Complicating cardiac failure
2. Precipitating cardiac failure
These are urgent situations requiring admission
1. Consider TOE guided DC Cardioversion
2. Itensify Rx: iv DFO: 24r x 7 days plus DFP (?)
3. Conventional long term management: aim to prevent
further attacks
1.
2.
3.
Malcolm Walker TIF 2012
Betablockers
Amiodarone (short to medium term)
Anticoagulation
Specific arrhythmia
AF – special circumstances
3. In iron loaded TM with good LV function
4. In non iron loaded TM with good function
These are non-urgent situations requiring
1. Consider TOE guided DC Cardioversion after 4 weeks
anticoagulation
2. Itensify chelation Rx: if iron overloaded
3. Conventional rate & rhythm control
1.
2.
Betablockers
Rate lowering calcium channel blockers
4. Anticoagulation with warfarin or new agents
Malcolm Walker TIF 2012
Specific arrhythmia
AF – long term prevention strategy
• Long term prevention strategies of AF
 Medication: generally poor at long term prevention
Effective drugs potentially too toxic (Amiodarone)
 Less toxic drugs often less effective (Beta-block, Flecainide)

Thalassaemia population may have an advantage,
if AF complicates iron overload. Removing iron
may effectively prevent AF for many years (?)
 Consider ablation and other therapies
Malcolm Walker TIF 2012
Catheter based ablation for AF
• Cardiac catheter based techniques
• Complex & time consuming (2 to 4hr)
• Often GA required
• Specialist EP cardiologists & service
• Success rates 70 to 80%
• Recurrence rates approx 15% at 1 year
• Risk of Stroke, cardiac perforation 1% to 2%
Complications and success rates may be
different for thalassaemia population
Catheter based ablation for AF
Malcolm Walker TIF 2012
Catheter based ablation for AF
Malcolm Walker TIF 2012
Catheter based ablation for AF
• Rhythm control by ablation
 General success rates 70% to 80% “cure”
 15% need second ablation
• In TM population
 Experience is young
 Anecdotal evidence of much higher recurrence
rates
Malcolm Walker TIF 2012
AF: Interventional techniques to
reduce stroke risk
• Left atrial appendage occluder
 Catheter based technique
 Reduces risk of stroke
• Structural defect closure
 Patent foramen ovale (PFO) closure

If patient has strong pro-thrombotic tendency
Malcolm Walker TIF 2012
Bradycardia & heart block in thalassaemia
• Complete heart block common in the past is
rare today
Malcolm Walker TIF 2012
Bradycardia & heart block in thalassaemia
• Complete heart block is rare
• Mandates the use of a pacemaker
 Historically this would prevent the use of cMR
forever!
Malcolm Walker TIF 2012
“Patients and the implanting community
deserve nothing less than devices that are
safe by design and not by chance.”
– J. Rod Gimbel, MD, FACC
Emanuel Kanal, MD, FACR
For more information visit:
http://www.medtronic.com/mrisurescan/
Malcolm Walker TIF 2012
4 chambers
LA
RA
Lead
Signal alteration
Malcolm Walker TIF 2012
LV
RV
cMR safe pacemakers
Malcolm Walker TIF 2012
Arrhythmia and thalassaemia
Conclusions
• Complex pathophysiology, which may be
changing as TM population ages
• Practical management issues largely revolve
around intensified chelation, as this may control
problem
• Role of EP techniques needs to be fully defined
• Devices need to be cMR compatible
Malcolm Walker TIF 2012